Carbonic anhydrase activators: activation of the archaeal beta-class (Cab) and gamma-class (Cam) carbonic anhydrases with amino acids and amines.
Activation of the archaeal beta-class (Cab) and gamma-class (Cam) carbonic anhydrases (CAs, EC 4.2.1.1) with a series of natural and non-natural amino acids and aromatic/heterocyclic amines has been investigated. Cab, Zn-Cam and Co-Cam showed an activation profile with natural, L- and D-amino acids very different of those of the alpha-class enzymes CA I, II and III. Most of these compounds showed medium efficacy as archaeal CA activators, except for D-Phe and L-Tyr which were effective Cab activators (K(A)s of 10.3-10.5 microM), 2-pyridylmethylamine and 1-(2-aminoethyl)-piperazine which effectively activated Zn-Cam (K(A)s of 10.1-11.4 microM) and serotonin, L-adrenaline and 2-pyridylmethylamine which were the best Co-Cam activators (K(A)s of 0.97-8.9 microM). We prove here that the activation mechanisms of the alpha-, beta-, and gamma-class CAs are similar, although the activation profiles with various compounds differ dramatically between these diverse enzymes.
Innocenti
Alessio
A
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
Zimmerman
Sabrina A
SA
Scozzafava
Andrea
A
Ferry
James G
JG
Supuran
Claudiu T
CT
D000588:Amines / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D001105:Archaea / Q000201:enzymology*; D002256:Carbonic Anhydrases / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D002384:Catalysis; D015394:Molecular Structure; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
D000588:Amines; D000596:Amino Acids; D014443:Tyrosine; D010649:Phenylalanine; D002256:Carbonic Anhydrases